Imatinib in combination with cytarabine as compared to Imatinib alone in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN51564734
• Date of registration: 07/06/2006
• Prospective Registration: No
• Primary sponsor: Dutch Haemato-oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON)
• Public title: Imatinib in combination with cytarabine as compared to Imatinib alone in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.
• Date of first enrolment: 08/05/2006
• Target sample size: 330
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN51564734
• Study type: Interventional
• Study design: A prospective randomized, parallel group, phase III study (Treatment)

Countries of recruitment

Netherlands

Contacts

• Name: J.J. Cornelissen

Key inclusion & exclusion criteria

Inclusion criteria: 1. Newly diagnosed patients with chronic myeloid leukemia (CML) in first chronic phase 2. Presence of Philadelphia chromosome or bcr-abl rearrangement
3. Age 18-65 years inclusive
4. World Health Organization (WHO) performance status 5. Written informed consent
Exclusion criteria: 1. CML in accelerated phase or blastic crisis as defined by the WHO criteria
2. Hepatic dysfunction (serum bilirubin >/= 2 x upper limit of normal [ULN], and/or alanine aminotransferase [ALAT] >/= 4 x ULN, and/or aspartate aminotransferase [ASAT >/= 4 x ULN)
3. Renal dysfunction (creatinine >/= 200 µmol/l or 2.3 mg/dl)
4. Severe cardiac dysfunction (New York Heart Association [NYHA] classification II-IV)
5. Severe pulmonary or neurological disease
6. Pregnant or lactating females
7. Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
8. Patients known to be human immunodeficiency virus (HIV)-positive
9. Patients with active, uncontrolled infections
10. Previous treatment other than hydroxyurea for 11. Male and female patients of reproductive potential who are not practicing effective means of contraceptio

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic myeloid leukemia
Cancer
Chronic myeloid leukemia

Intervention(s)

Patients meeting all eligibility criteria will be randomized between:
Arm A: imatinib given orally at a total dose of 800 mg daily until progression
Arm B: imatinib given orally at a total dose of 800 mg daily, combined with 2 successive cycles of intravenous ( i.v.) cytarabine 200 mg/m^2, at day 1-7, in cycles I and II, followed by imatinib monotherapy (800 mg daily) until progression

Primary Outcome(s)

Rate of major molecular response at 12 months from randomization

Secondary Outcome(s)

1. Rate and duration of major and complete molecular response
2. Rate and duration of major and complete cytogenetic response
3. Rate and duration of complete hematological response
4. Progression-free survival (i.e. time from registration to progression or death from any cause, whichever occurs first)
5. Overall survival measured from the time of registration. Patients still alive or lost to follow-up are censored at the date they were last known to be alive.
6. Toxicity
7. Actual dose-intensity of imatinib delivered
8. Incidence of mutations of abl-kinase domain

Secondary ID(s)

HO78

Source(s) of Monetary Support

Roche Nederland BV, Dutch Cancer Society, Amgen, Johnson and Johnson-Orthobiotech, Novartis Pharma B.V.